We have shown that in the rabbit infusion of norepinephrine (NE), 2 micrograms/min./kg, uniformly elicits a myocarditis and myofiber necrosis. These lesions were not significantly modified in animals pretreated with the beta-1 blocking agent practolol (4 mg/kg). Preliminary studies have suggested that the cardiomyopathy may result from alpha-receptor stimulation. In the proposed investigations, methoxamine will be infused using a protocol similar to that with NE. Arterial pressure and heart rate, blood gases, PH, hematocrit, and blood glucose concentrations will be measured. The animals will be sacrificed two days later. The hearts will be removed and histologic sections obtained for quantitative microscopic assessment of cardiac lesions. These animals will be compared with a group pretreated with the alpha-blocking agent phentoalamine. A third group will be infused with NE, but given phentoalamine 30 min. prior to the infusion to determine if the cardiomyopathy is related to the alpha-stimulating properties of NE. Insulin largely inhibits the appearance of NE cardiomyopathy. Effects of this hormone on the appearance of methoxamine lesions will be examined. Finally, a group of rabbits rendered diabetic with alloxan will be infused with methoxamine to determine if insulin-deficient animals are more sensitive to myocardial injury resulting from alpha-receptor stimulation.